RESUMO
PURPOSE: Post hoc analysis of the JAVELIN Bladder 100 trial of avelumab maintenance in locally advanced/metastatic urothelial carcinoma (la/mUC) to determine the interaction by programmed death ligand 1 (PD-L1) status for overall survival (OS), and additional analyses of survival per a different PD-L1 expression cutoff of ≥ 1% in tumor cells or immune cells (TC/IC). METHODS: JAVELIN Bladder 100 data were used for the analysis of the interaction by PD-L1 status (per cutoff used in the trial) for OS and, additionally, OS and progression-free survival (PFS) analyses per a different ≥ 1% TC/IC PD-L1 expression cutoff (Ventana SP263 assay). RESULTS: No significant interaction between treatment and PD-L1 status was observed for OS. Clinically meaningful and robust survival data were observed in favor of avelumab using the different ≥ 1% TC/IC PD-L1 expression cutoff. CONCLUSIONS: These results demonstrate the benefit of avelumab maintenance in la/mUC regardless of PD-L1 expression, consistent with approved labels.
Assuntos
Anticorpos Monoclonais Humanizados , Antígeno B7-H1 , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Antígeno B7-H1/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Intervalo Livre de Progressão , Feminino , Masculino , Antineoplásicos Imunológicos/uso terapêutico , Idoso , Pessoa de Meia-Idade , Quimioterapia de Manutenção , Taxa de SobrevidaRESUMO
BACKGROUND: Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. METHODS: We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. RESULTS: From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors" (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43-22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99-36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. CONCLUSION: Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). GOV IDENTIFIER: NCT01584297.
Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Cetoconazol/uso terapêutico , Esteroide 17-alfa-Hidroxilase/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Inibidores Enzimáticos , Células da Granulosa/metabolismo , Células da Granulosa/patologiaRESUMO
OBJECTIVES: The EORTC Quality of Life (QL) Group has developed a questionnaire (the EORTC IN-PATSAT32) to assess the satisfaction of cancer inpatients with hospitalbased care. In this study we assess the psychometric properties of the EORTC IN-PATSAT32 applied to a sample of Spanish patients. MATERIALS AND METHODS: Eighty cancer patients with different tumour sites completed the EORTC QLQ-C30 and EORTC IN-PATSAT32 questionnaires. Psychometric evaluation of the structure, reliability and validity was conducted. RESULTS: Multitrait scaling analysis showed that most itemscale correlation coefficients met the standards of convergent and discriminant validity. Cronbach's coefficients were good (0.77-0.97) for all scales except hospital access. Correlations between the scales and single items of the QLQ-C30 and EORTC IN-PATSAT32 were generally low. Correlations between the Oberst scales and an item on intention to recommend the hospital or ward to others with the EORTC IN-PATSAT32 were moderate. Patients with higher scores on the Oberst scales and the item on intention to recommend the hospital or ward showed higher satisfaction with care levels in all EORTC IN-PATSAT32 areas but one. CONCLUSIONS: The EORTC IN-PATSAT32 appears to be a reliable and valid instrument when applied to a sample of Spanish cancer patients. These results are in line with those of the EORTC validation study.